VOL. 10 No. 2 | May 2019

By Jon Holmlund

This past Tuesday, the Presidential Symposium at the 2018 Annual Meeting of the American Society of Hematology (ASH) addressed human gene editing. The speakers included NIH Director Dr. Francis Collins, who spoke about somatic gene editing. That’s the attempt to edit disease-causing genes in existing, fully formed individuals who have the disease in question, as treatment. It’s generally well-addressed by our current ethical principles for human subject research, and it’s easy to agree that it is an appropriate use of gene editing technology, which has become so widespread—and, indeed, largely uncontrollable—because of the recently-discovered, highly efficient, easy-for-scientists-to-use CRISPR-Cas9 system. The NIH has a specific Somatic Cell Gene Editing program.

Dr. Collins was followed by Dr. George Daley of Harvard, who presented a thoughtful case for proceeding with heritable gene editing—i.e., of germ cells (eggs and sperm) or, more likely, embryos, specifically during in vitro fertilization. The recent editing of twin babies, announced in Hong Kong, was highly irresponsible, he said—in agreement with the vast majority of expert and general public commentators. Fundamental principles of human subject research had been disregarded. We must do what we can to guard against “hubris.” Nonetheless, he agreed with the U.K.’s Nuffield Council opinion of earlier this year that ethical uses of human gene editing can be imagined. Specifically, rare, serious genetic diseases untreatable by other means would qualify. But rarity should not be a rigid requirement; there might be other genetic diseases for which future research would identify heritable gene editing as a viable if not preferred approach. A “stop sign” or “red light” should be erected at enhancement—e.g., trying to edit genes to get more muscular or smarter people. But this seems like a distant prospect. Dr. Daley ended by endorsing a statement of the recently-concluded international symposium on gene editing in Hong Kong: a “rigorous translational path” should be defined for human gene editing. In everyday English: steps to refine the technique in the laboratory should be taken, and steps needed to bring that work to the editing of people should be identified, in much the way that current regulated new drug development follows a series of well-defined steps.

But the actual translation should not go forward until there has been serious consideration of the societal and ethical concerns. Some such efforts are happening now, he said. I’ve blogged over the last few years about some of these, but you may not have heard of many, much less had a chance to contribute or had any way of thinking that concerns you might have would be properly represented. Indeed, as I have said on this blog earlier this year (see my March 29 post, for example), it’s hard to imagine how to conduct social deliberation of the scale required by the utterly revolutionary prospect of human gene editing. In a Q+A panel session, Dr. Collins asked Dr. Daley whether the answer to such deliberations might be “no”—might there be a decision not to proceed at all with editing human embryos? Dr. Daley said, “yes, of course,” but I wonder. For his part, Dr. Collins had sounded a highly cautionary note: Embryo editing raises serious safety concerns, issues of informed consent, and questions about what it is to be human, he had said. Perhaps its proper use would be so narrowly circumscribed that it really is not worth the trouble. “Bad cases make bad law,” as it were, he had said.

After my post of last week, an inquirer had wondered aloud whether someone contributing to this blog might be able to figure out how many embryos had been destroyed in the run-up to the Chinese twins’ birth, or, for that matter, for the other laboratory experiments done so far in human gene editing. Skeptical that such data exist anywhere, your correspondent nonetheless asked Dr. Daley in the Q+A whether there was any way reliably to estimate the “supply need” (I used that phrase) for human gametes or embryos in the course of the “rigid translational path.” Dr. Daley of course could not make any more precise estimate than “very many embryos” would have to be destroyed in the process. I must concur; I cannot see how a quantitative estimate could be made. He allowed that moral objection to this would be one of the issues with this work, and commented that in the U.K., plans are to issue licenses for the necessary embryo experiments as part of an attempt to regulate them.

But the emerging picture is that human embryos are “raw materials” supporting the “translational” development of heritable gene editing, much as starting chemicals are raw materials for the production of a new drug. That production process is governed by a panoply of regulations collectively referred to as “Good Manufacturing Practice,” a term that was applied to human gene editing more than once in the aforementioned ASH symposium.

I also asked whether the so-called “14-day rule” that scientists voluntarily follow as a time limit on human embryo research—i.e., don’t let them get more than 14 days old before killing them—would have to be relaxed. Dr. Daley thought not. I must say I wonder. If embryos could be maintained in the lab for more than 14 days—something that still is not technically feasible, but is being actively contemplated by scientists in the field—might someone not insist that their development be followed as long as possible before taking the step of trying to bring them to term—that is, to full pregnancy and birth?

Perhaps not. Unless more sophisticated “hatcheries” are developed, edited embryos would have to be implanted in a woman’s womb, after which there would be a progressively stronger presumption against aborting them, the older their gestational age. But such a presumption would not be absolute under current American law and jurisprudence. To be sure, the later a research abortion—currently prohibited in the U.S.—the greater a risk to a pregnant woman, not just the fetus being aborted.

And other intrepid actors, somewhere in the world, might well try to proceed outside a fully-regulated framework, purposefully setting up assessments at various gestational ages.

I must add that one liability of the line of thinking I have been taking here is that it might promote the misconception that the principal or even only reason to object to heritable human gene editing is a “pro-life, anti-abortion, religious” concern about the moral status of human embryos. Not so, although the status of the embryo is a critical consideration. There are lots of other reasons to object to this revolutionary development, and to say, as Dr. Collins suggested that “the answer should be ‘no.’”

#Bioethics News: In its decision to approve two drugs for orange and grapefruit trees, the E.P.A. largely ignored objections from the C.D.C. and the F.D.A., which fear that expanding their use in cash crops could fuel antibiotic resistance in humans. https://t.co/9hAvsohLvB